Methotrexate Induced Neurotoxicity And Reproductive Dysfunction: Role Of Honey And Bee Venom In Modulating Acetylcholine Esterase Activity, Reproductive Parameters And Histopathological Damage In Albino Rats

Abstract

Objective: Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent associated with adverse effects such as neurotoxicity and reproductive dysfunction. This study aimed to evaluate the protective effects of honey and bee venom on MTX-induced toxicity in male albino rats.

Methods: Thirty adult male rats were randomly assigned into five groups (n = 6 per group): normal control, MTX-treated, MTX + raw honey-treated, MTX + bee venom-treated, and MTX + raw honey + bee venom-treated. Raw Honey (1.2 g/kg, orally) and bee venom (0.5 mg/kg, intraperitoneally) were administered daily for 42 days, while MTX (5 mg/kg, intraperitoneally) was administered weekly once for 6 weeks. Evaluations included absolute and relative organ weights (brain and testis), sperm parameters (count, motility, viability), brain acetylcholinesterase (AChE) activity, and histopathological analysis of brain and testicular tissues.

Results: MTX administration significantly decreased organ weights and reproductive indices, and increased AChE activity and tissue damage (p < 0.0001). Treatment with honey and bee venom ameliorated these effects, with the combination therapy showing the most pronounced improvements across all parameters. Histopathological assessments confirmed the restoration of normal architecture in brain and testicular tissues in the treated groups.

Conclusion: Honey, especially when combined with bee venom, demonstrated antioxidant, anti-inflammatory, and neuroprotective properties that mitigated MTX-induced toxicity. These findings support the potential use of natural bioactive compounds as adjuvants to reduce the systemic side effects of chemotherapeutic agents like MTX.